Gold nanoparticles (GNPs), commonly known as colloidal gold, find an increasing number of potential biomedical applications, both in diagnostics and therapy of disease. The unique opto-electrical properties of GNPs, which can be defined by the presence of metallic cores and surface plasmons, have promoted wide use of GNPs in diagnostics. The spectral changes resulting from the particle size change or particle aggregation of the GNPs can be useful in designing systems for molecular recognition of biomolecules. In some applications, GNPs can be used as individual nano-sensors. Such nano-sensors can rely on binding of molecules to the GNPs surfaces and resultant plasmonic interactions for sensing changes in the environment.
However, there are significant problems with GNPs. Gold is not bio-inert, and mild-to-severe nephrotoxicity of gold-containing preparations have been found in various animals in the past. Bare GNPs present in a solution are typically unstable and will aggregate and precipitate out of the solution. Gold and silver/gold nanoparticles form stable colloidal suspensions in water only in the presence of a special stabilizer or a stabilizer with reducing properties that can be added during the synthesis of metallic nanoparticles. The most commonly used stabilizer/reducer is sodium citrate. Such colloidal suspensions collapse at high nanoparticle concentrations in the presence of sodium citrate. To prevent such colloidal solutions from becoming unstable, polymers (linear, diblock, triblock, or dendrimeric) have been used to coat the already-formed nanoparticles. The precursor metallic nanoparticles are usually obtained by using sodium citrate (Turkevich's method), which acts as a reducing/capping reagent. Another method for producing metallic nanoparticles (Martin's method, as well as similar but more complex Brust's methods) requires the use of sodium borohydride as a reducer and 1-dodecanethiol as a stabilizer. In the latter case, extraction into organic phase is required. However, the need in a long-chain aliphatic thiol stabilizer severely limits the ability to add new or several functionalities to the surface of the nanoparticles. Additionally, the use of such compounds can require an additional derivatization step in the synthesis of the GNPs.
It is generally believed that a combination of small particle size and a protective layer on the surface of GNPs improves their biocompatibility. The latter is usually provided by adsorbing and/or chemically orienting polymers [23] on the surface of nanoparticles generating a layer that is sterically and chemically protective. There are prior water-based GNP synthesis strategies that utilize a combination of reducing/gold colloid capping polymers leading to GNP preparations of various diameters, and a variety of surface properties [24]. Of these polymers, very few provide a stable and relatively biologically inert coating, which is required for the GNPs to escape recognition and sequestration by macrophages [25]. A high molecular weight deacetylated chitosan has been recently suggested as a potential replacement for more commonly used protective polymer PEG-thiol [26, 27]. Though the use of the latter does result in stabilized and relatively biologically inert nanoparticles [28], unlike chistosan, PEG-coated GNPs are unstable in the presence of reduced glutathione [27, 29]. However, unlike chitosan, [30-32] methoxypoly(ethylene glycol) does not bind, nor does it activate, complement components unless terminal hydroxyl is exposed on PEG chains [33].
Thus, novel nanoparticles and methods of preparing such nanoparticles that overcome these and other problems associated with conventional nanoparticles and synthesis methods are needed.